Benzophenones are very useful in organic synthesis in general and in the pharmaceutical industry in particular. Although it is common to prepare benzophenones by Friedel-Crafts benzoylation, known methods of preparing 2,5-dichlorobenzophenones from 1,4-dichlorobenzene have had very limited success and have been characterized by low conversion, low yield and difficulty in purification due to isomeric contamination of the desired 2,5-dichlorobenzophenone. Moreover, previous attempts to prepare 2,5-dichlorobenzophenones from 1,4-dichlorobenzene commonly have used nitrobenzene as a solvent. Nitrobenzene is highly toxic and its use is regulated. All of these factors limit the possibility of commercial-scale preparation of 2,5-dichlorobenzophenones from 1,4-dichlorobenzene.
In one example of the prior methods just described, after heating dichlorobenzene and benzoyl chloride with aluminum chloride for 49 hours at 150.degree. to 170.degree. C., 2,5-dichlorobenzophenone was obtained in only 20% yield. (Th. de Crauw, Rec. Trav. Chim. Pay Bas 50, 767, (1931)). In another case, 2,5-dichlorobenzophenone was obtained in 0.8% yield, together with appreciable amounts of other isomers, after running the reaction in nitrobenzene for 10 hours at 100.degree. C. (P. A. Goodman et al., J. Chem. Soc. (C) 2452, (1968)). Other unsuccessful examples can be found in the literature. See, e.g., J. Ganzmuller, J. Prakt. Chem. 138, 311, (1933); p. H. Gore et al., Zh. Org. Khim., 1145, (1967) 10% yield; M. Godfrey et al., Tetrahedron, 32, 843, (1976) (0.8% yield).
Higher yields of pure 2,5-dichlorobenzophenones have been obtained by starting with 2,5-dichlorobenzoyl chloride. (B. M. Zarnegar, Canadian Patent No. 1,153,369, granted to Mobil Oil Corporation U.S.A.). This aroyl chloride is not commercially available and has to be synthesized from expensive 2,5-dichlorobenzoic acid. Moreover, when 2,5-dichlorobenzoyl chloride reacts with substituted benzenes, e.g., toluene, regiosteric isomers usually cannot be avoided. Such a synthetic scheme is unattractive.
Accordingly, a need exists for an inexpensive method for preparing isomerically pure 2,5-dichlorobenzophenone and substituted analogs from 1,4-dichlorobenzene in high yield.